Mutations in the CLCN2 gene encoding ClC-2, a chloride channel implicated in brain ion and water homeostasis, have been recently associated with a rare autosomal recessive leukoencephalopathy, characterized by specific MRI findings caused by chronic white matter edema.
1Case report. A 42-year-old Italian man born from consanguineous parents was admitted for a subclinical leukoencephalopathy discovered during a previous assessment for infertility. He had azoospermia, demonstrated by repeated semen analyses since age 36 years, but noninvasive azoospermia workup had normal results (appendix e-1 on the Neurology ® Web site at Neurology.org), and he refused testicular biopsy. At age 39 years, pituitary MRI was performed because repeat hormone screening had revealed slightly increased prolactin (26.6 ng/mL [normal 4.04-15.2]). There was no conclusive evidence of pituitary adenoma, but, despite the lack of neurologic symptoms, white matter signal abnormalities were incidentally found in the brain, with a pattern consisting of prominent T2-weighted hyperintensity in the internal capsule posterior limbs, midbrain cerebral peduncles, and middle cerebellar peduncles. No decreased apparent diffusion coefficient (ADC) values were found in the areas of abnormal T2-weighted signal. Prolactin normalized under cabergoline therapy (0.125 mg/wk), but semen analysis still showed azoospermia. Over a 2-year follow-up, the leukodystrophic pattern remained unchanged, and the patient continued to have no neurologic symptoms. When he came to our attention, neurologic examination showed only a positive palmomental reflex, inconstant minimal postural hand tremor, increased deep tendon reflexes, and bilateral Hoffmann sign. No Babinski sign was noted. Repeat brain MRI findings are shown in the figure. Magnetic resonance spectroscopy and pituitary MRI were unremarkable as well as hormone screening (he was still treated with cabergoline). Neuro-ophthalmologic examination, including computerized visual field testing, neuropsychological assessment, EEG, somatosensory evoked potentials, and EMG with nerve conduction studies, had normal results. Motor evoked potentials showed only upper limb central motor conduction times at the upper limit of the normal range (7.0 ms [normal ,7
